Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells

被引：62

作者：

Bai, Qianming ^{[1
,2
]}

Xu, Leyuan ^{[1
]}

Kakiyama, Genta ^{[1
]}

Runge-Morris, Melissa Ann ^{[3
]}

Hylemon, Phillip B. ^{[4
]}

Yin, Lianhua ^{[2
]}

Pandak, William M. ^{[1
]}

Ren, Shunlin ^{[1
]}

机构：

[1] Virginia Commonwealth Univ, McGuire Vet Affairs Med Ctr, Dept Med, Richmond, VA 23249 USA

[2] Fudan Univ, Dept Physiol & Pathophysiol, Shanghai Med Coll, Shanghai 200032, Peoples R China

[3] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48207 USA

[4] Virginia Commonwealth Univ, McGuire Vet Affairs Med Ctr, Dept Microbiol Immunol, Richmond, VA 23249 USA

来源：

ATHEROSCLEROSIS | 2011年 / 214卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Cytosolic sulfotransferase (SULT2B1b); 25-Hydroxycholesterol (25HC); 25-Hydroxycholesterol-3-sulfate (25HC3S); Oxysterol sulfation; Lipid metabolism; BILE-ACID SYNTHESIS; ORPHAN NUCLEAR RECEPTORS; PRIMARY RAT HEPATOCYTES; IN-VIVO; CHOLESTEROL; METABOLISM; OXYSTEROL; EXPRESSION; LIVER; TRANSCRIPTION;

D O I：

10.1016/j.atherosclerosis.2010.11.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: 25-Hydroxycholesterol (25HC) and its sulfated metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), regulate certain aspects of lipid metabolism in opposite ways. Hence, the enzyme for the biosynthesis of 25HC3S, oxysterol sulfotransferase (SULT2B1b), may play a crucial role in regulating lipid metabolism. We evaluate the effect of 25HC sulfation on lipid metabolism by overexpressing the gene encoding SULT2B1b in human aortic endothelial cells (HAECs) in culture. Methods and results: The human SULT2B1b gene was successfully overexpressed in HAECs following infection using a recombinant adenovirus. HPLC analysis demonstrated that more than 50% of H-3-25HC was sulfated in 24 h following overexpression of the SULT2B1b gene. In the presence of 25HC, SULT2B1b overexpression significantly decreased mRNA and protein levels of LXR, ABCA1, SREBP-1c, ACC-1, and FAS, which are key regulators of lipid biosynthesis and transport; and subsequently reduced cellular lipid levels. Overexpression of the gene encoding SULT2B1b gave similar results as adding exogenous 25HC3S. However, in the absence of 25HC or in the presence of T0901317, synthetic liver oxysterol receptor (LXR) agonist, SULT2B1b overexpression had no effect on the regulation of key genes involved in lipid metabolism. Conclusions: Our data indicate that sulfation of 25HC by SULT2B1b plays an important role in the maintenance of intracellular lipid homeostasis via the LXR/SREBP-1c signaling pathway in HAECs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：350 / 356

页数：7

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